Proinflammatory Th17 cells are expanded and induced by dendritic cells in spondylarthritis‐prone HLA–B27–transgenic rats

Glatigny, Simon; Fert, Ingrid; Blaton, Marie A.; Lories, Rik; Araujo, Luiza M.; Chiocchia, Gilles; Bréban, Maxime

doi:10.1002/art.33321

Cited by 121 publications

(114 citation statements)

References 46 publications

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“…More recently, investigations conducted in the B27-transgenic rat model for spondyloarthritis showed that Th17 cells contribute to both intestinal and joint inflammation; IL-17-producing cells were expanded in mesenteric as well as in popliteal lymph nodes (16). In agreement with this, we found early expression of IL-17 in popliteal and inguinal lymph nodes of mice undergoing S. Enteritidis enterocolitis.…”

Section: Discussionsupporting

confidence: 78%

Salmonella enterica Induces Joint Inflammation and Expression of Interleukin-17 in Draining Lymph Nodes Early after Onset of Enterocolitis in Mice

et al. 2012

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Section: Discussionsupporting

confidence: 78%

Salmonella enterica Induces Joint Inflammation and Expression of Interleukin-17 in Draining Lymph Nodes Early after Onset of Enterocolitis in Mice

et al. 2012

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“…[6][7][8][9][10] Several lines of evidence have identified the interleukin-17 pathway as a promising therapeutic target in spondyloarthritis. [11][12][13][14][15][16][17] Indeed, numbers of interleukin-17-producing cells are elevated in the circulation and target tissues in patients with ankylosing spondylitis. [14][15][16][17][18] Secukinumab is a fully human, anti-interleukin-17A monoclonal antibody with proven efficacy in psoriasis.…”

Section: Secukinumab In Ankylosing Spondylitismentioning

confidence: 99%

“…(%) Psoriasis 8 (6) 4 (3) 7 (6) 6 (8) 6 (8) 8 (11) Inflammatory bowel disease 2 (2) 6 (5) 2 (2) 3 (4) 0 2 (3) Uveitis 15 (12) 25 (20) 22 (18) 11 (15) 10 (14) 13 (18) No previous anti-TNF therapy -no. (%)…”

Section: Secukinumab In Ankylosing Spondylitismentioning

confidence: 99%

Secukinumab, an Interleukin-17A Inhibitor, in Ankylosing Spondylitis

et al. 2015

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“…Another hypothesis is that ERAP1 polymorphisms could affect gene expression level (19). In the present study, we investigated the influence of ERAP-1 genetic makeup on its quantitative expression, at both the messenger RNA (mRNA) and protein levels, as well as enzymatic activity in monocyte-derived dendritic cells (DCs), antigen-presenting cells relevant to the study of ERAP-1 function and potentially involved in SpA pathogenesis (27)(28)(29)(30)(31)(32). We also accounted for the marked linkage disequilibrium.…”

mentioning

confidence: 99%

ERAP1 Gene Expression Is Influenced by Nonsynonymous Polymorphisms Associated With Predisposition to Spondyloarthritis

Costantino

Talpin

Evnouchidou

et al. 2015

Arthritis & Rheumatology

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Objective Several polymorphisms in ERAP1 are strongly associated with susceptibility to spondyloarthritis (SpA). The combination of rs17482078, rs10050860, and rs30187 results in the construction of 3 major haplotypes that are associated with SpA (the “protective” haplotype T/T/C, the “neutral” haplotype C/C/C, and the “susceptibility” haplotype C/C/T). The aim of the present study was to determine whether such haplotypes might affect endoplasmic reticulum aminopeptidase 1 (ERAP‐1) messenger RNA (mRNA) expression, protein level, and/or enzymatic activity in antigen‐presenting cells, a type of cell that is potentially relevant to disease pathogenesis. Methods Monocyte‐derived dendritic cells (DCs) were generated in 2 cohorts (a discovery cohort and a replication cohort) comprising a total of 23 SpA patients and 44 healthy controls. Lymphoblastoid B cell lines were established from individuals who were homozygous for the risk, the neutral, or the protective ERAP1 haplotype, respectively. In those samples, we investigated the relationship between ERAP1 haplotypes and mRNA expression level. We also used Western blot analysis to measure the relative protein expression of ERAP‐1 and a fluorogenic assay to measure its enzymatic activity. Results In monocyte‐derived DCs, there was a strong association between ERAP1 haplotypes and the ERAP‐1 mRNA expression level, with higher levels in subjects harboring the susceptibility haplotype (P = 0.001 and P = 5.6 × 10−7 in the discovery and replication cohorts, respectively). In lymphoblastoid B cell lines, we observed a significant correlation between haplotype risk score and ERAP1 transcript or protein level (P = 0.003, ρ = 0.92 for both). Enzymatic activity followed a similar trend both in monocyte‐derived DCs and in lymphoblastoid B cell lines. Conclusion These data provide strong evidence that SpA‐associated ERAP1 polymorphisms affect the level of gene expression in antigen‐presenting cells. How increased production/activity of ERAP‐1 may influence susceptibility to SpA remains to be determined.

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Proinflammatory Th17 cells are expanded and induced by dendritic cells in spondylarthritis‐prone HLA–B27–transgenic rats

Cited by 121 publications

References 46 publications

Salmonella enterica Induces Joint Inflammation and Expression of Interleukin-17 in Draining Lymph Nodes Early after Onset of Enterocolitis in Mice

Salmonella enterica Induces Joint Inflammation and Expression of Interleukin-17 in Draining Lymph Nodes Early after Onset of Enterocolitis in Mice

Secukinumab, an Interleukin-17A Inhibitor, in Ankylosing Spondylitis

ERAP1 Gene Expression Is Influenced by Nonsynonymous Polymorphisms Associated With Predisposition to Spondyloarthritis

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